I. The Anatomy of a Healthy Heart
The heart (see FIG. 1) is slightly larger than a clenched fist. It is a double (left and right side), self-adjusting muscular pump, the parts of which work in unison to propel blood to all parts of the body. The right side of the heart receives poorly oxygenated (“venous”) blood from the body from the superior vena cava and inferior vena cava and pumps it through the pulmonary artery to the lungs for oxygenation. The left side receives well-oxygenation (“arterial”) blood from the lungs through the pulmonary veins and pumps it into the aorta for distribution to the body.
The heart has four chambers, two on each side—the right and left atria, and the right and left ventricles. The atriums are the blood-receiving chambers, which pump blood into the ventricles. The ventricles are the blood-discharging chambers. A wall composed of fibrous and muscular parts, called the interatrial septum separates the right and left atriums (see FIGS. 2 to 4). The fibrous interatrial septum is, compared to the more friable muscle tissue of the heart, a more materially strong tissue structure in its own extent in the heart.
An anatomic landmark on the interatrial septum is an oval, thumbprint sized depression called the oval fossa, or fossa ovalis (shown in FIG. 4), which is a remnant of the oval foramen and its valve in the fetus. It is free of any vital structures such as valve structure, blood vessels and conduction pathways. Together with its inherent fibrous structure and surrounding fibrous ridge which makes it identifiable by angiographic techniques, the fossa ovalis is the favored site for trans-septal diagnostic and therapeutic procedures from the right into the left heart, and attachment of structure to heart tissue. Before birth, oxygenated blood from the placenta was directed through the oval foramen into the left atrium, and after birth the oval foramen closes.
The synchronous pumping actions of the left and right sides of the heart constitute the cardiac cycle. The cycle begins with a period of ventricular relaxation, called ventricular diastole. The cycle ends with a period of ventricular contraction, called ventricular systole.
The heart has four valves (see FIGS. 2 and 3) that ensure that blood does not flow in the wrong direction during the cardiac cycle; that is, to ensure that the blood does not back flow from the ventricles into the corresponding atria, or back flow from the arteries into the corresponding ventricles. The valve between the right atrium and the right ventricle is the tricuspid valve. The valve between the left atrium and the left ventricle is the mitral valve. The pulmonary valve is at the opening of the pulmonary artery. The aortic valve is at the opening of the aorta.
At the beginning of ventricular diastole (i.e., ventricular filling) (see FIG. 2), the aortic and pulmonary valves are closed to prevent back flow from the arteries into the ventricles. Shortly thereafter, the tricuspid and mitral valves open (as FIG. 2 shows), to allow flow from the atriums into the corresponding ventricles. Shortly after ventricular systole (i.e., ventricular emptying) begins, the tricuspid and mitral valves close (see FIG. 3)—to prevent back flow from the ventricles into the corresponding atriums—and the aortic and pulmonary valves open—to permit discharge of blood into the arteries from the corresponding ventricles.
The opening and closing of heart valves occur primarily as a result of pressure differences. For example, the opening and closing of the tricuspid valve occurs as a result of the pressure differences between the right atrium and the right ventricle. During ventricular diastole, when ventricles are relaxed, the return of carbon dioxide rich blood from the superior and inferior vena cava into the right atrium causes the pressure in the atrium to exceed that in the ventricle. As a result, the tricuspid valve opens, allowing blood to enter the ventricle. As the ventricle contracts during ventricular systole, the intraventricular pressure rises above the pressure in the atrium and pushes the tricuspid valve shut.
The tricuspid and mitral valves are defined by fibrous rings of collagen, each called an annulus, which forms a part of the fibrous skeleton of the heart. The annulus provides attachments for the three cusps or leaflets of the tricuspid valve (called the anterior, posterior, and septal leaflets) and the two cusps or leaflets of the mitral valve (called the anterior and posterior leaflets). The leaflets receive chordae tendineae from more than one papillary muscle. In a healthy heart, these muscles and their tendinous chords support the mitral and tricuspid valves, allowing the leaflets to resist the high pressure developed during contractions (pumping) of the left and right ventricles. FIG. 5 shows the chordae tendineae and papillary muscles in the right ventricle that support the tricuspid valve.
As seen in FIGS. 5 and 6, the tricuspid valve complex consists of the three leaflets, chordae tendineae, two main papillary muscles, the tricuspid annulus, and the right atrial and right ventricular myocardium. Successful valve function depends on the integrity and coordination of these components. Of the three tricuspid valve leaflets, the anterior leaflet is generally the largest and the posterior leaflet is notable for the presence of multiple scallops. The anterior papillary muscle provides chordae to the anterior and posterior leaflets. The medial papillary muscle provides chordae to the posterior and septal leaflets. The septal wall gives chordae to the anterior and septal leaflets (note that there is no formal septal papillary muscle as with the anterior and posterior papillary muscles). The small septal wall leaflet is fairly fixed and there is little room for compensation/movement if the free wall of right ventricle/tricuspid annulus should dilate.2 Dilation of the tricuspid annulus therefore primarily occurs in the anterior/posterior (mural) aspect (see FIG. 7).3 
Other important factors influencing the degree of tricuspid regurgitation include the right ventricular preload, afterload and right ventricular function. The tricuspid annulus is dynamic and there is approximately a nineteen percent reduction in annular circumference (approximately thirty percent reduction in annular area) with atrial systole.4, 5 
A 3-dimensional (3D) echocardiographic study has shown that the tricuspid annulus has a complicated 3D geometry (see FIG. 8), distinct from the simpler “saddle shape” of the mitral annulus. In patients with functional tricuspid regurgitation, the tricuspid annulus is generally more dilated in the septal-lateral direction, resulting in a more circular shape than in healthy subjects.4 
As FIGS. 2 and 3 show, the anterior portion of the mitral valve annulus is intimate with the non-coronary leaflet of the aortic valve. As FIGS. 2 and 3 also show, the mitral valve annulus is also near other critical heart structures, such as the circumflex branch of the left coronary artery (which supplies the left atrium, a variable amount of the left ventricle, and in many people the SA node) and the AV node (which, with the SA node, coordinates the cardiac cycle).
Also in the vicinity of the posterior mitral valve annulus is the coronary sinus and its tributaries. These vessels drain the areas of the heart supplied by the left coronary artery. The coronary sinus and its tributaries receive approximately 85% of coronary venous blood. The coronary sinus empties into the posterior of the right atrium, anterior and inferior to the fossa ovalis (see FIG. 4). A tributary of the coronary sinus is called the great cardiac vein, which courses parallel to the majority of the posterior mitral valve annulus, and is superior to the posterior mitral valve annulus by an average distance of about 9.64+/−3.15 millimeters (Yamanouchi, Y, Pacing and Clinical Electrophysiology 21(11):2522-6; 1998).
II. Characteristics and Causes of Tricuspid Valve Dysfunction
When the left ventricle contracts after filling with blood from the left atrium, the walls of the ventricle move inward and release some of the tension from the papillary muscle and chords. The blood pushed up against the under-surface of the mitral leaflets causes them to rise toward the annulus plane of the mitral valve. As they progress toward the annulus, the leading edges of the anterior and posterior leaflet come together forming a seal and closing the valve. In the healthy heart, leaflet coaptation occurs near the plane of the mitral annulus. The blood continues to be pressurized in the left ventricle until it is ejected into the aorta. Contraction of the papillary muscles is simultaneous with the contraction of the ventricle and serves to keep healthy valve leaflets tightly shut at peak contraction pressures exerted by the ventricle.
In a healthy heart (see FIG. 9), the dimensions of the tricuspid valve annulus create an anatomic shape and tension such that the leaflets coapt, forming a tight junction, at peak contraction pressures. Where the leaflets coapt at opposing sides of the annulus are called the leaflet commissures.
Valve malfunction can result from the chordae tendineae (the chords) becoming stretched, and in some cases tearing. When a chord tears, the result is a leaflet that flails. Also, a normally structured valve may not function properly because of an enlargement of or shape change in the valve annulus, as shown in FIG. 7. This condition is referred to as a dilation of the annulus and generally results from heart muscle failure. In addition, the valve may be defective at birth or because of an acquired disease.
Regardless of the cause, tricuspid valve dysfunction can occur when the leaflets do not coapt at peak contraction pressures (see FIG. 10). As shown, the coaptation line of the three leaflets is not tight at ventricular systole. As a result, an undesired back flow of blood from the right ventricle into the right atrium can occur.
The general causes of tricuspid valve pathology are secondary (74%), rheumatic (11%), congenital (9%), or other (endocarditis, leaflet tear/prolapse, chordal rupture, papillary muscle rupture [rare], or myxomatous degeneration of the tricuspid valve).6 In North America, the most common cause of tricuspid valve disease is tricuspid regurgitation (TR) secondary to left heart pathology, such as mitral valve disease/regurgitation and left heart failure.7 This is felt to result in right-sided pressure overload which results in right ventricular chamber enlargement, tricuspid annular dilation, and resultant TR. This mechanistic cascade led to the concept that treatment of the left-sided abnormality will result in secondary improvement or amelioration of TR. However, Dreyfus et al. have made the point that because this paradigm advocates treatment of proposed “primary” lesion only (i.e., mitral valve disease), this approach will not directly correct tricuspid annular dilation or right ventricular function, the major determinants of functional TR.
Without treatment, TR may become worse over time leading to severe symptoms, biventricular heart failure and death.8 It has been shown in a large retrospective echocardiographic analysis of 5223 subjects by Nath et al., that independent of echo-derived pulmonary artery systolic pressure, left ventricular ejection fraction, inferior vena cava size, and right ventricular size and function, survival is worse for patients with moderate and severe TR than for those with no TR (TR graded using Framingham Heart Study criteria).9 In this series, the prevalence of TR in a Veterans Administration population was: no TR, 11.5%; mild TR, 68.8%; moderate TR, 11.8%; and severe TR, 3.8%.
The prevalence of TR from pacemaker leads is as yet poorly defined, but is likely more significant and prevalent than currently perceived. In a recent report by Kim et al., the effect of transtricuspid permanent pacemaker (PPM) or implantable cardiac defibrillator (ICD) leads on 248 subjects with echocardiograms before and after device placement was studied. The authors found that TR worsened by 1 grade or more after implant in 24.2% of subjects, and that TR worsening was more common with ICDs than PPMs with baseline mild TR or less.10 Residual and recurrent TR after surgical tricuspid annuloplasty is common and occurs in 14% of patients early after operation for all types of annuloplasty.8 Five years after successful TV repair, 42% of patients with a pacemaker had severe TR, almost double those without the device. This suggests removing the transtricuspid lead and replacing it with an epicardial lead at the time of TV surgery may reduce late repair failure.1 
There are numerous reports describing the presence of TR in patients undergoing surgery for mitral regurgitation. The prevalence of TR in the postoperative period depends to some degree on the mechanism of MR. Matsuyama et al. reported in a study of 790 patients that only 16% of patients who underwent nonischemic (i.e., degenerative) mitral valve surgery without tricuspid valve surgery developed 3 to 4+ TR at 8 year follow-up.11 Conversely, TR appears to be prevalent in patients undergoing mitral valve repair for functional ischemic mitral regurgitation. In the series by Matsunaga et al., of 70 patients undergoing MV repair for functional ischemic mitral regurgitation, 30% (21/70) of patients had at least moderate TR before surgery. In the postoperative period, the prevalence of at least moderate TR increased over time from 25% at less than one year, 53% at 1 to 3 year, and 74% at greater than 3 year follow-up.12 
Significant tricuspid valve insufficiency may also contribute to a poor hemodynamic result even after successful mitral valve repair. In one early series by King et al., patients requiring subsequent tricuspid valve surgery after MV surgery had high early and late mortality. The authors encouraged a policy of liberal use of tricuspid annuloplasty at initial mitral valve surgery.13 Accordingly, 50-67% of patients undergoing surgery for mitral valve disease have been reported to undergo concomitant surgical TV repair or replacement.1, 6 Investigators have also attempted to identify specific patient subsets that should have TV repair/replacement at the time of MV repair/replacement.
It has been proposed that at the time of MV repair, the presence of tricuspid annular dilation (≥70 mm measured intraoperatively) even in the absence of significant TR should be an indication for TV annuloplasty. This paper also showed that TR increased by at least 2 grades in 45% of the patients who received isolated MVR, supporting the notion that tricuspid dilation is an ongoing, progressive process that often warrants preemptive surgical treatment.14 
In the series by Singh and colleagues, tricuspid valve repair appears to result in improved mid-term survival (up to 10 years after surgery, primarily due to higher perioperative mortality with replacement) as compared with TV replacement, although there was no difference in valve-related mortality or need for TV reoperation.) The authors hypothesized that the higher perioperative mortality with replacement may have been due to a rigid object (TV valve) in a deformable low-pressure cavity (right ventricle, RV), with resultant RV dysfunction and perioperative low output state. Although patients in this series had less recurrent TR with replacement vs. repair (95% vs. 62% had mild or less TR at most recent echocardiographic follow-up), there was no difference in functional class in either group.
Other surgical series have shown that successful tricuspid valve repair (primarily when combined with other valve surgeries) resulted in a significant improvement in recurrent TR, survival, and event-free survival.
III. Prior Treatment Modalities
Multiple percutaneous therapies are now available or under development for the treatment of aortic, mitral and pulmonic valve disease. In contrast, there has been little discussion regarding percutaneous approaches to tricuspid valve repair. Despite the fact that tricuspid regurgitation (TR) can result in significant symptoms, it is rare for patients to be referred for isolated surgical tricuspid valve repair given the morbidity and mortality of surgery.
The presence of tricuspid regurgitation is often underdiagnosed and surgically ignored. Re-operations for recurrent TR are also felt to be high risk surgical procedures (˜37% in-hospital mortality) and are therefore not offered to many patients.1 In this era of percutaneous valve repair and replacement, the relevance and potential need for the percutaneous treatment of TR should be considered.
The need remains for a simple, cost effective, and less invasive devices, systems, and methods for treating dysfunction of a heart valve, e.g., in the treatment of tricuspid valve regurgitation.